Practice question

Troponin heterotrimer every 38 nanometer along thin filament alongside tropomyosin provides calcium dependent switch. Subunits: TnT 30 to 35 kilodalton tropomyosin binding anchoring complex, TnI 21 to 24 kilodalton inhibitory binding actin blocking myosin in diastole, TnC 18 kilodalton calcium binding sensor homologous to calmodulin containing four EF hand helix loop helix motifs. N terminal low affinity regulatory sites I II bind calcium transiently during systole with Kd 5 micromolar triggering activation, affinity modulated by magnesium competition, C terminal high affinity structural sites III IV bind calcium magnesium constitutively with Kd nanomolar stabilizing complex. Calcium binding to N lobe induces opening exposing hydrophobic patch that binds switch peptide residues 148 to 158 of TnI removing C terminal inhibitory mobile domain from actin. This releases tropomyosin steric block exposing myosin binding sites permitting cross bridge cycling. Mutation TnC G159D reduces calcium affinity blunting contractility, TN-M nonexistent. Thus TnC uniquely senses calcium transient translating electrical signal into mechanical contraction and force generation.